Browse the evidence

Rapid and substantial weight reduction, such as that achieved by bariatric surgery or certain medications, may result in greater reductions in lean muscle mass compared to gradual weight reduction.

If you are undergoing rapid weight loss (e.g., surgery or strong medications), prioritize resistance training and adequate protein intake to protect your muscle mass. Monitor your body composition, not just scale weight, to ensure you are losing fat, not muscle.

GLP-1 receptor agonists increase the risk of gallbladder disease, including cholelithiasis and cholecystitis, through mechanisms involving cholecystokinin (CCK) suppression, altered bile acid receptor signaling (FXR/TGR5), and disrupted gut-brain pathways, leading to bile stasis and gallstone formation.

If you are taking a GLP-1 agonist (like semaglutide or liraglutide), be aware that you have a higher risk of gallbladder problems, especially if you are taking higher doses or losing weight rapidly. Watch for symptoms like severe abdominal pain, nausea, or fever, and report them to your doctor immediately. Your doctor may monitor you more closely or adjust your treatment plan to mitigate this risk.

Biased agonism of GLP-1R and GIPR (favoring cAMP over beta-arrestin recruitment) yields superior glucose lowering, food intake suppression, and weight loss compared to unbiased agonism.

Current GLP-1/GIP drugs that favor cAMP signaling (biased) appear to offer better and longer-lasting glucose control and weight loss than those that do not. This is likely due to the drug staying on the receptor longer without being internalized. While this is proven in mice, it suggests that drug design matters for efficacy, not just receptor activation.

Naltrexone/Bupropion is not recommended for individuals with obesity and established atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) due to potential hemodynamic stress and lack of outcome data.

If you have obesity and established heart disease or heart failure, naltrexone/bupropion is not recommended because it can increase heart rate and blood pressure, potentially worsening your condition. Safer, proven alternatives are available.

Lixisenatide and high-dose efpeglenatide (6 mg/week) are associated with a statistically significant increase in hearing loss events compared to controls, whereas other GLP-1 receptor agonists and SGLT2 inhibitors do not demonstrate this elevated risk.

If you are taking Lixisenatide or high-dose Efpeglenatide, be aware of a potential increased risk of hearing loss. This risk is not seen with other GLP-1 drugs like Semaglutide or Dulaglutide in this analysis. Report any sudden hearing changes to your doctor immediately, but do not stop your medication without consulting them, as the absolute risk (NHH ~757) is relatively low.

Current randomized controlled trials of nutrient-stimulated hormone-based therapies (NuSHs) for obesity predominantly fail to assess nutritional and functional outcomes, focusing almost exclusively on body weight.

If you are participating in or designing a NuSH trial, you must include nutritional and functional assessments (body composition, muscle strength, bone health) alongside weight. Relying solely on weight masks potential risks like sarcopenia and bone loss.

Current NuSH trials rarely assess bone health, despite the known risk of bone mass reduction associated with significant weight loss.

If you are on NuSHs, ask your doctor about bone density scans, especially if you are post-menopausal or elderly. Ensure adequate calcium and vitamin D intake, as weight loss can compromise bone strength.

Protein restriction (specifically low-protein, high-carbohydrate diets) extends lifespan and improves metabolic health in model organisms, likely through mechanisms distinct from or overlapping with calorie restriction, such as elevated FGF21.

In model organisms, restricting protein (while keeping calories normal) extends lifespan and improves metabolic health, partly by boosting FGF21. However, this comes at the cost of muscle mass. For humans, high protein is generally recommended for muscle maintenance, but excessive intake might increase mortality risk. The optimal protein intake likely balances longevity benefits with the need to preserve physical resilience, suggesting a moderate approach rather than extreme restriction or excess.

Individuals with greater personal success in weight loss without medication exhibit higher obesity stigma and less favorable attitudes toward anti-obesity medications.

Healthcare providers should recognize that patients who have successfully lost weight through diet and exercise may be skeptical of or stigmatizing toward GLP-1 medications. Counseling should validate their success while explaining that biological factors can persist despite lifestyle efforts, making medication a valid and effective tool for others.

Male sex, older age (≥65 years), lower socioeconomic status (lower income, less education, higher area deprivation), and lack of insurance are associated with significantly lower odds of receiving anti-obesity medication (AOM) prescriptions and metabolic and bariatric surgery (MBS).

If you are male, older, or have limited income/insurance, you face significant systemic barriers to accessing obesity treatments like GLP-1s or surgery. This is not a reflection of your medical need but of socio-economic disparities. Seek providers who are aware of these disparities and advocate for coverage options or financial assistance programs.

Second-generation oral contraceptive pill phase (active vs. inactive) does not influence muscle protein synthesis or myofibrillar proteolysis at rest or in response to resistance exercise.

If you take second-generation birth control pills, you can train for muscle growth without worrying about your pill cycle. Your muscles build and break down protein at the same rate whether you are on the active pills or the placebo week. Focus on your training and nutrition; the pill phase does not matter for your results.

Adding the long-acting PYY3-36 analogue PYY1875 (1.0 mg/week) to semaglutide (2.4 mg/week) yields only modest, non-clinically meaningful additional weight loss in people with obesity and is poorly tolerated due to gastrointestinal adverse events.

For individuals already on semaglutide, adding PYY1875 at 1.0 mg weekly provides only a small, likely unnoticeable additional weight loss benefit while significantly increasing the risk of gastrointestinal side effects like nausea. The 2.0 mg dose was not tolerated. Current evidence suggests this combination is not a viable strategy for improving weight loss outcomes due to poor tolerability and lack of clinical significance.

Using percent body weight loss as the sole target for obesity management is not ideal because it is often not feasible or sustainable for most participants and fails to capture holistic health outcomes.

Stop fixating on a specific percentage of weight loss as the only measure of success. For many people, achieving even a modest weight loss is not sustainable. Instead, focus on patient-centered outcomes like improved blood pressure, better glycemic control, and increased quality of life, which can be achieved through various lifestyle changes regardless of the final number on the scale.

Physiological levels of GIP promote fat accumulation and insulin resistance in the context of high-fat diets and aging, acting as a 'thrifty hormone' that stores nutrients.

In the context of a high-fat diet, your body's natural GIP hormone helps store fat and may contribute to insulin resistance. This is why blocking GIP (antagonism) can help reduce obesity, while stimulating it pharmacologically (agonism) works through different mechanisms like appetite suppression in the brain.

Initiating insulin glargine in patients with type 2 diabetes is associated with a higher risk of gastroparesis, intestinal obstruction, and all-cause mortality compared to initiating SGLT2 inhibitors.

If you are considering insulin glargine for type 2 diabetes, know that it is associated with a higher risk of gastroparesis, intestinal obstruction, and death compared to SGLT2 inhibitors. This does not mean insulin is bad, but it highlights the importance of choosing the right medication for your specific health profile. If you are at risk for GI issues, SGLT2 inhibitors might be a safer choice.

Knockout of the microprotein encoded by Adipocyte-smORF-1183 significantly impairs adipocyte differentiation and reduces lipid droplet formation.

This research identifies a specific, previously unknown protein (Adipocyte-smORF-1183) in mouse fat cells that is essential for storing fat. Knocking out this protein reduces fat storage by about half in these cells. While this is a fundamental biological discovery that could lead to future therapies for obesity, it is currently limited to cell culture models and does not yet translate to a direct human treatment or lifestyle intervention.

Higher circulating estrogen levels in women are predictive of increased rates of nausea and vomiting when taking GLP-1 receptor agonists, and estrous cycle phase modulates drug sensitivity in female mice.

Your risk of side effects from GLP-1 drugs may fluctuate with your menstrual cycle, peaking when estrogen is highest. While this paper used mice, human data suggests higher estrogen levels correlate with more nausea. Tracking your cycle might help you and your doctor anticipate and manage side effects.

Daily supplementation with 0.6 g/kg body weight of whey protein does not enhance body composition, core muscle endurance, or joint flexibility adaptations in trained women performing 10 weeks of Pilates training, despite increasing total daily protein intake to ~1.78 g/kg.

If you are a trained woman doing Pilates regularly, adding whey protein supplements on top of your normal diet will not make you lose more fat, gain more muscle, or improve your flexibility compared to just doing the training. Focus on consistent training and adequate whole-food protein intake rather than buying supplements.

Males in the US have consistently higher diabetes incidence and prevalence than females across all age groups, with a significant disparity that becomes more pronounced in older cohorts.

Men in the US are diagnosed with diabetes more often than women, and this gap widens with age. This may be partly due to biological factors and partly due to less frequent healthcare engagement. Men should prioritize regular screening and not delay care due to cultural norms.

Usual intakes of animal and plant protein are not adversely associated with all-cause, cardiovascular disease, or cancer-related mortality risk in adults.

You do not need to restrict your protein intake, whether from animal or plant sources, to avoid increasing your risk of death from all causes, heart disease, or cancer. The data suggests that typical protein intakes within recommended ranges are safe and not linked to higher mortality.

GLP-1RA treatment induces distinct molecular changes in skeletal muscle proteome (upregulation of mitochondrial proteins) compared to calorie restriction, despite similar weight loss and muscle mass changes.

This finding is primarily mechanistic and suggests GLP-1s may improve muscle metabolic efficiency (mitochondrial function) beyond just weight loss, though this does not currently translate to a specific user action beyond standard treatment.

GLP-1 receptor agonists and MC4R modulators are emerging therapeutic strategies that target hypothalamic pathways to treat metabolic diseases.

Current treatments for obesity and diabetes, such as GLP-1 receptor agonists, work by targeting specific pathways in the hypothalamus. This highlights the importance of central nervous system mechanisms in these conditions and supports the use of these medications as effective treatments.

GLP-1 receptor agonists slow renal disease progression and reduce albuminuria in patients with diabetic kidney disease, although evidence is less robust than for SGLT2 inhibitors.

If you have diabetic kidney disease, GLP-1 receptor agonists may help slow kidney damage and reduce protein in your urine. While there is less data on their kidney benefits compared to SGLT2 inhibitors, they are still considered valuable. Discuss with your doctor if they are appropriate for you, especially if you have cardiovascular risks.

Orforglipron is associated with a dose-dependent increase in gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation) and treatment discontinuation rates, particularly at doses of 12 mg and higher.

While effective, orforglipron often causes stomach problems like nausea, vomiting, and diarrhea, especially at higher doses (12 mg and above). These side effects are the main reason people stop taking the medication. Patients should be aware that higher doses provide more weight loss but also carry a higher risk of stopping treatment due to discomfort. Starting at a lower dose and titrating slowly may help manage these side effects.